We have previously demonstrated that Con A or LPS activated human peripheral blood monocytes produce collagenase through a prostaglandin dependent mechanism. Our recent studies have concentrated on the effect of biologically defined molecules such as recombinant interferon-Gamma (rIFN-Gamma) and recombinant granulocyte-monocyte colony stimulating factor (rGM-CSF) on the production of PGE2 and collagenase by monocytes. While the addition of rIFN-Gamma alone to monocytes had no effect on PGE2 and collagenase synthesis, when added to Con A stimulated monocytes rIFN-Gamma caused a dose dependent inhibition of both products. Collagenase synthesis was restored in rIFN-Gamma treated cultures by the addition of exogenous PGE2 which indicated that IFN-Gamma regulated collagenase production by its effect on arachidonic acid metabolism. In contrast to IFN-Gamma, our preliminary findings with rGM-CSF indicate that this molecule stimulates PGE2 and collagenase synthesis by human monocytes. Studies on the role of the immune system in bone resorption have focussed on our previous observation that spleen cells from osteopetrotic (op) rats have reduced proliferative capacity to mitogens when compared to normal littermates. Our recent experiments have shown that while IL-1 levels of spleen cell cultures from normal and op rats were similar, the IL2 levels of Con A or PHA stimulated spleen cells from op rats were decreased by 70%. However, the inability of op spleen cells to proliferate to Con A could not be overcome by the addition of normal spleen cells supernatants, purified IL2 or arachidonic acid metabolite inhibitors. Based on monoclonal staining, similar percentages of suppressor and helper T cells were found in normal and op spleens. Thus, the immunosuppression in the op rats may be the consequence of decreased ability to produce IL2, a more efficient suppressor T cell population and/or non-T cell populations which suppress proliferation. Furthermore, these defects in immunologic responses may contribute to the inability of the op rats to regulate bone metabolism.